The ω-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial--rationale and design.

Abstract

Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a "real-world" population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.

• Authors: Dariush Mozaffarian, Roberto Marchioli, Tim Gardner, Paolo Ferrazzi, Patrick O'Gara, Roberto Latini, Peter Libby, Federico Lombardi, Alejandro Macchia, Richard Page, Massimo Santini, Luigi Tavazzi, Gianni Tognoni
• Journal: American heart journal (Am Heart J) Vol. 162 Issue 1 Pg. 56-63.e3 (Jul 2011) ISSN: 1097-6744 [Electronic] United States
• PMID: 21742090 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, American Recovery and Reinvestment Act, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Mosby, Inc. All rights reserved.

Chemical References

• Fatty Acids, Omega-3

Topics

• Administration, Oral
• Adolescent
• Atrial Fibrillation (etiology, physiopathology, prevention & control)
• Cardiac Surgical Procedures (adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Fatty Acids, Omega-3 (administration & dosage)
• Follow-Up Studies
• Heart Diseases (surgery)
• Humans
• Postoperative Complications
• Treatment Outcome